Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 8 March 2016 to 21 April 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Stabilisation: in water undergoes hydrolysis
Specific details on test material used for the study:
- Analytical purity: 92%

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Cmdb: WI; outbred
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Experimental Medicine Centre at the Medical University in Białystok
- Age at study initiation: 9-week-old males and 15-week-old females
- Weight at study initiation: Males average body weight was 272.6 g, females average body weight was 225.2 g
- Housing: The animals were housed in plastic cages covered with wire bar lids. The dimensions of the cages were 58 x 37 x 21 cm (length x width x height). After the application of the test item, each animal was housed individually. After the removal of the test item from the animals’ skin, there were five rats in one cage. Each sex was kept separately.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: The animals were quarantined and observed daily for 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 – 23 °C
- Humidity (%): 30 – 50%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 30.03.2016 To:13.04.2016

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunks, 30-45cm2 was shaved, patch size 6 x 6 cm
- % coverage: he area of skin treated with the test item was 10% of the body surface area
- Type of wrap if used: The patches were laid on the prepared skin and covered with PVC foil (no contact with skin). An elastic bandage and a sticking plaster were used to make a circular protecting band.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test item was removed using water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg b.w.

VEHICLE
- Amount(s) applied (volume or weight with unit): The test item, in form of powder was moistened of a few drops of water (to provide better contact with the skin).
Duration of exposure:
24h
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: evaluation of general condition twice a day or once a day (on days off) during the 14-day experiment. Body weights of the animals were determined on days 0 (directly before the application of the test item), 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs - Detailed clinical observations were made on the application day (day 0) at hourly intervals up to 5 hours. From the 1st to the 14th day of the experiment, the detailed clinical observations were performed once a day.

Results and discussion

Preliminary study:
Not carried out
Effect levels
Key result
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the experiment.
Clinical signs:
The animals did not exhibit any general clinical signs. No pathological changes on the treated skin were noticed.
Body weight:
During the first week of the experiment, body weight loss in two females was observed. During the 14-day experiment, body weight loss in two females was observed. During the 14-day experiment body weights of the remaining animals increased.
Gross pathology:
The gross examination did not reveal any pathological changes in the examined animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of the test item was > 2000 mg/kg bw in rats.
Executive summary:

The acute dermal toxicity of the test item was determined in accordance to the OECD Guideline 402 with GLP. The test item at a single dose of 2000 mg/kg b.w. was applied to the shaved dorsal area of the trunks of 5 males and 5 females rats for 24 hours. After the application of the test item, the animals were observed for 14 days. General and detailed clinical observations of all animals were performed daily during the entire experiment. Body weights of the animals were determined on days 0 (directly before the application of the test item), 7, and 14. After the 14-day observation period, the animals were euthanized, dissected, and subjected to detailed gross examinations. The animals did not exhibit any general clinical signs. No pathological changes on the treated skin were noticed. All animals survived the experiment. These results indicate that the acute dermal LD50 of the test item is > 2000 mg/kg bw in rats.